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Analysis of long non-coding RNA expression profiles in disuse osteoporosis using microarray and bioinformatics.
1Department of Joints, Tianjin Hospital, Tianjin University, Tianjin, China.
Journal of Biological Regulators and Homeostatic Agents
|July 23, 2021
Summary
Disuse osteoporosis (DOP) is a consequence of spaceflight and immobility. This study identifies key long non-coding RNAs (lncRNAs) and potential therapeutic compounds, revealing new mechanisms for DOP development and treatment.
Area of Science:
- Biomedical Sciences
- Genomics
- Space Medicine
Background:
- Disuse osteoporosis (DOP) is a significant health concern resulting from prolonged immobility, such as in spaceflight or spinal cord injuries.
- Bone marrow mesenchymal stem cells (BMSCs) are crucial for bone homeostasis, and their dysregulation in osteogenic differentiation can lead to orthopedic diseases.
- The precise molecular mechanisms underlying DOP remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular mechanisms of disuse osteoporosis (DOP) by analyzing gene expression data.
- To identify differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) involved in DOP.
- To discover potential therapeutic targets and compounds for treating DOP.
Main Methods:
- Utilized R's limma package to identify differentially expressed mRNAs and lncRNAs from Gene Expression Omnibus (GEO) datasets (GSE100930, GSE17696).
- Constructed a coding-non-coding gene co-expression (CNC) network to analyze interactions between lncRNAs and mRNAs.
- Performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and Connectivity Map (CMap) analysis for drug discovery.
Main Results:
- Identified 2,212 differentially expressed mRNAs (DEmRNAs) and 22 differentially expressed lncRNAs (DElncRNAs).
- The CNC network highlighted GSNAS1, SNHG12, and EPB41LA4A-AS1 as key lncRNAs potentially regulating DOP.
- Connectivity Map analysis identified scoulerine, kinetin riboside, and dexanabinol as potential therapeutic agents for DOP.
Conclusions:
- Discovered a novel mechanism for bone marrow mesenchymal stem cell lineage shifts under microgravity, contributing to DOP.
- Established a link between protein-coding mRNAs and ncRNAs in the pathogenesis of DOP.
- The findings offer potential avenues for developing new therapeutic strategies for disuse osteoporosis.
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